Heretofore, for producing quinazolin-4-one derivatives from anthranilic acid derivatives, the following methods are known.
1) A method of producing 6-iodoquinazolin-4-one by reacting 5-iodoanthranilic acid and formamidine acetate under reflux in glacial acetic acid (for example, see Patent Reference 1); 2) a method of producing quinazolin-4-one by reacting ammonium formate and methyl anthranilate in the presence of formamide (for example, see Non-Patent Reference 1); 3) a method of producing quinazolin-4-one by reacting anthranilic acid and formamide in the absence of a catalyst (for example, see Non-Patent Reference 2); 4) a method of producing a quinazolin-4-one derivative by reacting an anthranilic acid derivative and an orthoformate in the presence of ammonia (for example, see Patent Reference 2); 5) a method of producing a quinazolin-4-one derivative by reacting an anthranilic acid derivative and an orthoformate in the presence of ammonium acetate (for example, see Patent Reference 3); 6) a method of producing a 6,7-dioxyquinazoline derivative by reacting a 4,5-dioxyanthranilate derivative and formamide, using formic acid or monobromoacetic acid as an acid catalyst or using an alkali metal carbonate as a basic catalyst (for example, see Patent Reference 4).
However, the method 1) of Patent Reference 1 has a problem in that expensive formamidine acetate must be used excessively as the nitrogen source and the carbon source for the quinazoline skeleton.
The method 2) of Non-Patent Reference 1 requires high-temperature and long-lasting reaction at 175° C. for 4 hours, and the yield of the obtained quinazolin-4-one is only at most 70%.
The method 3) of Non-Patent Reference 2 uses inexpensive formamide as the nitrogen source and the carbon source for the quinazoline skeleton; and the reaction with no catalyst at 130° C. for 2.5 hours gives an yield of 83. Thus, the production method is improved over the method of Non-Patent Reference 1, but the yield must be further enhanced in industrial application.
The method 4) of Patent Reference 2 uses ammonia as the nitrogen source, and uses an orthoformate as the carbon source.
According to the method, the reaction may be attained in the absence of a catalyst, but the method is problematic in that ammonia and further an expensive orthoformate must be used excessively.
The method 5) of Patent Reference 3 uses an ammonium carboxylate as the nitrogen source and uses an orthoformate as the carbon source, in which the reaction may be attained in the absence of a catalyst; however, the method is also problematic in that an expensive orthoformate must be used excessively therein.
The method 6) of Patent Reference 4 uses formamide as the nitrogen source and the carbon source for the quinazoline skeleton in producing a 6,7-dioxyquinazoline derivative; and using as a catalyst, an acid catalyst of formic acid or monobromoacetic acid or a basic catalyst of an alkali metal carbonate under a reaction temperature condition at 130° C., this produces a relatively good result of an yield of 90%; however, the reaction time is from 6 to 7 hours and is long, and this requires further improvement for industrial application.
As in the above, the conventional methods involve various problems that must be overcome, and are therefore not satisfactory.    [Patent Reference 1] JP-T 10-505600    [Patent Reference 2] JP-A 2003-183262    [Patent Reference 3] WO03/064399    [Patent Reference 4] JP-A 2002-338550    [Non-Patent Reference 1] B. R. BAKER, JOSEPH P. JOSEPH, ROBERTE. SCHAUB, FRANCIS J. McEVOY and JAMES H. WILLIAMS; J. Org. Chem., 18, 138 (1953)    [Non-Patent Reference 2] Christoph SEGER, Srunya VAJRODAYA, Harald GREGER, and Otmar HOFER; Chem. Pharm. Bull., 46(12) 1926-1928 (1998)